Fragmentation of the Golgi into small vesicles is a requirement for cellular division. It has been observed that treatment with a structurally interesting marine natural product, macfarlandin E, causes irreversible fragmentation of the Golgi, without causing delocalization of the resulting fragments. The first goal of this research is a chemical synthesis of macfarlandin E, which in itself would be an important contribution to an unusual class of marine spongian metabolites. The key transformations of the proposed chemistry are a conjugate addition to set two adjacent stereocenters (one being quaternary) and a intramolecular trapping of a oxocarbenium ion to build a unique 2,7-dioxabicyclo[3.2.1]octan-3-one scaffold found in several spongian natural products. Additionally, the synthesis allows for preparation of analogs containing biotin affinity tags and coumarin moieties for investigation and isolation of the Golgi proteins responsible for vesiculation and localization. The second goal of the research is to identify the biological target of macfarlandin E and determine its role in the regulation of vesiculation and localization of the Golgi. Understanding the components responsible for Golgi behavior would not only be an important contribution to Golgi biology, but it is the first step toward a more complete understanding of the cellular processes leading up to mitosis. The proposed research involves the chemical synthesis of a marine natural product, macfarlandin E, and its analogs. Preliminary work indicates macfarlandin E causes an unusual and interesting fragmentation of the Golgi aparatus in mammalian cells without delocalization of the fragments. These compounds will be used as chemical agents for the investigation of the nature of Golgi fragmentation. [unreadable] [unreadable] [unreadable]